Neonatal herpes simplex virus (HSV) infection can be a life threatening disease associated with high mortality and morbidity. Infection of the newborn with HSV is usually the consequence of intrapartum contact with infected maternal genital secretions. Infection can also be transmitted in utero or, infrequently, as a consequence of postnatal acquisition of HSV-1 by contact with infected individuals. We hypothesize that the treatment with high dose acyclovir will decrease mortality and morbidity of CNS or disseminated neonatal HSV infection. Specific aims of this protocol are: 1) To determine whether high dose acyclovir can further decrease morbidity and mortality of CNS or disseminated neonatal HSV infection both acutely and on long-term follow-up. 2) To determine if high dose acyclovir chemotherapy is safe and tolerated in the newborn, the following will be monitored: a) biochemical and bone-marrow parameters of host function (SGOT, BUN, Creatinine, CBC with differential, platelet count, and urinalysis, etc.); b) host antibody response (total HSV antibodies by ELISA and antibodies to specific polypeptides); and c) adverse effects both acutely and on long-term follow-up. 3) To determine if resistance to antiviral medication develops. 4) To amplify disease classification for babies with neonatal HSV infection for purposes of predicting prognosis. 5) To determine whether there is a change in viral excretion patterns in patients receiving high dose acyclovir. 6) To determine whether HSV-DNA in the CSF predicts long-term neurologic outcome. 7) To determine whether specific HSV DNA in the CSF following completion of treatment is indicative of insidious reactivation of virus in the brain.